Diabetes treatment has advanced rapidly over the past decade, with new drugs and technologies developed and translated into clinical care. Many of these treatments affect the kidney, are affected by chronic kidney disease (CKD), or carry both effects. In addition, new data have been published on foundational elements of care for people with diabetes and CKD, including lifestyle, ascertainment of glycemia, glycemic targets, and use of renin-angiotensin system (RAS) inhibitors. Providers and patients rightly ask how to apply the new treatments and integrate them into tailored existing care paradigms.
KDIGO has initiated a new clinical practice guideline to help guide medical management for people with diabetes and CKD. The goal of the new clinical practice guideline is to provide evidence-based recommendations for the care of people with diabetes and CKD. The guideline arose from a KDIGO Controversies Conference held in 2015 that outlined critical areas in need of evidence-based recommendations (1). The scope of the guideline was then refined by the KDIGO diabetes and CKD guideline writing group, with input through open commentary from the broad community engaged in managing diabetes and CKD.
The new guideline will take a comprehensive approach, covering lifestyle, glycemia assessment and targets, use of medications that target both glycemia and other intermediate targets, self-management, and systems of care (see box). The guideline is designed to apply to people with diabetes and any stage of CKD, from elevated urine albumin excretion and normal estimated GFR (eGFR) to severely reduced eGFR to ESKD treated with dialysis or kidney transplantation, highlighting the aspects of care that are common across the CKD spectrum and also those that should differ by severity of CKD. Similarly, the guideline will address care for people with both type 1 and type 2 diabetes, highlighting common and differential approaches where appropriate. The guideline will be informed by a systematic literature review performed by an expert evidence review team, focusing on high-level evidence from clinical trials.
New drugs will be addressed by this new diabetes and CKD guideline. Three new classes of drugs are revolutionizing diabetes care: sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors (2). All three classes reduce blood glucose, with a low risk of hypoglycemia. In addition, SGLT2 inhibitors and GLP-1 receptor agonists have shown substantial benefits in terms of cardiovascular and kidney outcomes (Table 1). These benefits were first demonstrated in large cardiovascular outcomes trials that were mandated by regulatory agencies to ensure cardiovascular safety of new diabetes drugs. SGLT2 inhibitors and GLP-1 receptor agonists proved to be not only safe but beneficial. In each of these drug classes, several specific drugs reduced cardiovascular events in high-risk populations (2). SGLT2 inhibitors also substantially reduced GFR loss in secondary analyses (3)—an effect confirmed in the recent CREDENCE trial (4). GLP-1 receptor agonists may also have renal benefits (5). However, all of these drugs do have adverse effects, most are restricted below certain eGFR thresholds and in kidney failure, and combinations with other glucose-lowering drugs remain poorly developed (3). Therefore, further guidance is needed on the implementation of these promising new drugs in clinical nephrology practice.
Summary of the benefits and harms of SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors, by class, as observed in large, placebo-controlled clinical outcomes trials
Perkovic V, et al. Management of patients with diabetes and CKD: Conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int 2016; 90:1175–1183.
Davies MJ, et al. Management of hyperglycemia in type 2 diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41:2669–2701.
Perkovic V, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380:2295–2306.
Tuttle KR. SGLT2 inhibitor and incretin mimetic therapy for type 2 diabetes and chronic kidney disease. Lancet Diabetes Endocrinol 2019; 7:414–415.
American Diabetes Association. 7. Diabetes Technology: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019; 42 [Suppl 1]:S71–S80.